Hepatic encephalopathy is a neuropsychiatric syndrome associated with liver damage from alcoholism, hepatitis and cirrhosis. Numerous metabolic derangements are found in patients with hepatic encephalopathy, including hyperammonemia, elevations in serum short-chain fatty acid concentrations, and alterations in brain neurotransmitter concentrations. Short-chain fatty acids are known to cause coma and hyperammonemia in experimental animals, and may represent a major cause of encephalopathy. The present proposal would evaluate the role of short-chain fatty acids in producing some of the central nervous system derangements seen in patients with hepatic encephalopathy. The following areas will be studied: 1) effect of the short-chain fatty acid octanoate on regional brain concentrations of octopamine, dopamine, and norepinephrine; #2) effect of octanoate on regional cerebral blood flow and brain glucose metabolism; and 3) role of carnitine in protecting the brain from octanoate-induced changes. Results of these studies will help to elucidate some of the pathogenetic mechanisms related to hepatic encephalopathy and may provide insight into a potential new treatment of this disorder.